Chronic Myocardial Infarction is a Substrate for Bradycardia-Induced Spontaneous Tachyarrhythmias and Sudden Death in Conscious Animals

Introduction: Patients with bradycardia can have severe tachyarrhythmias but it is unclear whether bradycardia alone can induce arrhythmias or whether an additional substrate is necessary. While several animal models of ventricular tachycardia (VT) exist, no model has been reported to mimic the clin...

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Published inJournal of cardiovascular electrophysiology Vol. 17; no. 2; pp. 189 - 197
Main Authors KILLINGSWORTH, CHERYL R., WALCOTT, GREGORY P., GAMBLIN, TRACY L., GIROUARD, L.V.T., STEVEN D., SMITH, WILLIAM M., IDEKER, RAYMOND E.
Format Journal Article
LanguageEnglish
Published 350 Main Street , Malden , MA 02148-5018 , USA , and 9600 Garsington Road , Oxford OX4 2DQ , UK Blackwell Publishing Inc 01.02.2006
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Summary:Introduction: Patients with bradycardia can have severe tachyarrhythmias but it is unclear whether bradycardia alone can induce arrhythmias or whether an additional substrate is necessary. While several animal models of ventricular tachycardia (VT) exist, no model has been reported to mimic the clinical condition of spontaneous VT and sudden cardiac death (SCD) in the presence of bradycardia and chronic myocardial infarction (MI) in large animals without manipulation of the autonomic nervous system. We tested the hypothesis that MI and bradycardia cause more spontaneous sustained VT than does bradycardia alone. Methods and Results: Sheep (42–56 kg) underwent atrioventricular (AV) node catheter ablation alone (n = 5) or AV node ablation and 150 minutes of angioplasty balloon occlusion of the left anterior descending coronary artery (n = 9). An implantable cardioverter defibrillator delivered rescue shocks and demand pacing at 90 beats per minute for the first week and at 40 beats per minute thereafter. Electrograms were continuously radiotelemetered and recorded for 6 weeks. Acute post‐MI VT disappeared by day 4. The sudden bradycardia on day 8 triggered numerous premature ventricular contractions (PVCs) and episodes of sustained VT lasting >30 seconds during the next 5 weeks. There were 43 episodes of sustained VT and no spontaneous ventricular fibrillation (VF) with bradycardia alone. However, in the presence of both MI and bradycardia there were 970 episodes of VT/VF (P < 0.05) and three deaths at days 13, 15, and 34. The average 24‐hour count of PVCs was similar at day 7 between the two groups but by days 11 and 40, the PVC counts were 35 times and 4 times greater, respectively, in the presence of bradycardia and chronic MI compared to bradycardia alone. No significant difference in the incidence of PVCs was detected because of large individual variation between the two groups (P = 0.21). A high PVC count did not appear to predict SCD. Conclusion: The combination of MI and bradycardia secondary to AV node ablation in sheep produces a higher incidence of VT than bradycardia alone, suggesting that this preparation can serve as a model for the study of VT and sudden cardiac death.
Bibliography:ArticleID:JCE336
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This study was supported by the National Institutes of Health Research Grant HL67961 (R.E.I., W.M.S.), by an American Heart Association Grant‐in‐Aid (C.R.K.), and by Guidant Corp.
Manuscript received 2 June 2005; Revised manuscript received 16 September 2005; Accepted for publication 20 September 2005.
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ISSN:1045-3873
1540-8167
DOI:10.1111/j.1540-8167.2005.00336.x